HIV/AIDS, killed 2.8 million persons in 2005, continues to be a major public health problem throughout the world. In the U.S. alone, approximately 40,000 persons become infected with HIV each year. Highly active antiretroviral combination therapy (HAART) has significantly reduced the number of AIDS deaths by 70% since 1996, and has changed the clinical profile of HIV infection from a sub-acute lethal to a chronic ambulatory disease. However, HIV-infected patients experience more mucosal opportunistic infections, more dental caries, and severe periodontal diseases, even after HAART, suggesting that compromised oral micro-environment within the oral cavity is a consequence of the viral infection. The long-term goal of this research is to elucidate the association among the innate host defense system, HIV infection, HAART, and oral microbiota. The objectives of the proposed study are to define the difference in oral microbiota between HIV-infected and non-infected individuals and to determine the effect of subsequent HAART on the dynamic changes of the microbial community in the oral cavity. Our central hypothesis is that HIV infection decreases the level of overall microbial colonization and diversity in the oral cavity and that HAART alters the microbiota so compromised. A corollary hypothesis is that the changes in microbial diversity in HIV+ individuals lead to an increase in cariogenic and periodontal bacteria, resulting in an increase in caries and periodontal disease. To test these hypotheses we will measure the colonization of (a) total cultivable microbes;(b) total Candida spp.;(c) total streptococci;and (d) total lactobacilli in saliva of HIV infected and noninfected subjects;examine the microbial diversity using the 16S rDNA-based approach;, and determine the association among specific salivary proteins of known involvement in HIV infection, specific cariogenic and periodontopathogenic bacterial colonization, and oral health assessments. The findings of this study will provide new insight into whether HIV infection causes changes in oral microbiota and salivary protein profiles favoring the development of caries and periodontal diseases and may the development of specific antibiotic therapy to prevent the adverse change in the microbiota and to decrease susceptibility to other infections